1-cyclohexyl-3,4-dihydroisoquinoline derivatives and pharmaceutical compositions containing them

Abstract

The invention relates to new 1-cyclohexyl-3,4-dihydroisoquinoline derivatives of the formula (I) <IMAGE> (I) wherein R1 and R2 each independently represents hydrogen, hydroxyl or alkoxy having from 1 to 6 carbon atoms, X is oxygen and Z is a =CH2 or =CH-COOR3 group, in which R3 is hydrogen or alkyl having from 1 to 6 carbon atoms; or X represents an =NR4 group, in which R4 is hydrogen or hydroxyl, and Z is a =CH-CN, =CH2 or =CH-COOR3 group, in which R3 is as defined above, and acid addition salts thereof. The compounds of formula (I) are pharmaceutically active, in particular show antispasm, analgesic, gastric acid secretion inhibiting, sedative and hypnotic activity and effectively reduce the alcoholic narcosis time. According to a further aspect of the invention there is provided a process for the preparation of these compounds. The invention further relates to pharmaceutical compositions containing them as active ingredient.

We claim: 
     
       1. A 1-Cyclohexyl-3,4-dihydroisoquinoline derivative of the formula (I) ##STR6## wherein R 1  and R 2  each independently represents hydrogen, hydroxyl or alkoxy having from 1 to 6 carbon atoms, X is oxygen and   Z is a ═CH 2  or ═CH--COOR 3  group, in which R 3  is hydrogen or alkyl having from 1 to 6 carbon atoms; or   X represents an ═NR 4  group, in which R 4  is hydrogen or hydroxyl, and   Z is a ═CH--CN, ═CH 2  or ═CH--COOR 3  group, in which R 3  is as defined above, and an acid addition salt thereof.     
     
     
       2. A compound of the formula (I), in which R 1  and R 2  are both methoxy or ethoxy, while X, Z, R 3  and R 4  are as defined in claim 1. 
     
     
       3. A compound selected from the group consisting of 1-(4'-oxo-cyclohexyl)-3,4-dihydro-6,7-dimethoxyisoquinoline,   1-[(3'-methoxycarbonyl-4'-oxo)-1-cyclohexyl]-3,4-dihydro-6,7-dimethoxyisoquinoline,   1-[(3'-ethoxycarbonyl-4'-oxo)-1-cyclohexyl]-3,4-dihydro-6,7-dimethoxyisoquinoline,   1-[(3'-cyano-4'-imino)-1-cyclohexyl]-3,4-dihydro-6,7-dimethoxyisoquinoline,   1-(4'-cyclohexyloxime)-3,4-dihydro-6,7-dimethoxyisoquinoline,   1-{[3'-(methoxycarbonyl)-4'-imino]-1-cyclohexyl}-3,4-dihydro-6,7-dimethoxyisoquinoline and hydrochlorides of these compounds.     
     
     
       4. A pharmaceutical composition comprising as an active ingredient an effective amount of at least one compound of the formula (I) of claim 1 or a physiologically acceptable salt thereof, in association with a pharmaceutical carrier and/or excipient. 
     
     
       5. A pharmaceutical composition comprising an effective amount of at least one compound as set forth in claim 3 or a hydrochloride thereof in association with a pharmaceutical carrier and/or excipient.